Submissions for variant NM_000329.3(RPE65):c.496-4G>A

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 3

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Leber Congenital Amaurosis/early Onset Retinal Dystrophy Variant Curation Expert Panel, ClinGen	RCV003768909	SCV004697390	likely benign	RPE65-related recessive retinopathy	2024-02-19	reviewed by expert panel	curation	NM_000329.3(RPE65):c.496-4G>A is a non-coding variant near the junction of intron 5 with exon 6. This variant is present in gnomAD v.2.1.1 at a GrpMax allele frequency of 0.001437, with 59 alleles / 24910 total alleles in the African/African-American population, which is higher than the ClinGen LCA / eoRD VCEP BS1 threshold of >0.0008 (BS1). The splicing impact predictor SpliceAI gives a delta score of 0.01 for either acceptor loss or acceptor gain, which is below the ClinGen LCA / eoRD VCEP recommended threshold of <0.1 and does not predict an impact on splicing (BP4). In summary, this variant meets the criteria to be classified as likely benign for RPE65-related recessive retinopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen LCA / eoRD VCEP: BS1, BP4. (VCEP specifications version 1.0.0; date of approval 09/21/2023).
Invitae	RCV000945902	SCV001091973	likely benign	Leber congenital amaurosis 2; Retinitis pigmentosa 20	2024-01-31	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001275285	SCV001460285	uncertain significance	Leber congenital amaurosis	2020-04-30	no assertion criteria provided	clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.